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Intermittent versus continuous first-line treatment for HER2-negative metastatic breast cancer: the Stop & Go study of the Dutch Breast Cancer Research Group (BOOG)

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Abstract

Purpose

We determined if intermittent first-line treatment with paclitaxel plus bevacizumab was not inferior to continuous treatment in patients with HER2-negative, advanced breast cancer.

Methods

Patients were randomized to 2 × 4 cycles or continuous 8 cycles of paclitaxel plus bevacizumab, followed by bevacizumab maintenance treatment until disease progression or unacceptable toxicity. The primary endpoint was overall progression-free survival (PFS). A proportional-hazards regression model was used to estimate the HR. The upper limit of the two-sided 95% CI for the HR was compared with the non-inferiority margin of 1.34.

Results

A total of 420 patients were included with well-balanced characteristics. In the intention-to-treat analysis, median overall PFS was 7.4 months (95% CI 6.4–10.0) for intermittent and 9.7 months (95% CI 8.9–10.3) for continuous treatment, with a stratified HR of 1.17 (95% CI 0.88–1.57). Median OS was 17.5 months (95% CI 15.4–21.7) versus 20.9 months (95% CI 17.8–24.0) for intermittent versus continuous treatment, with a HR of 1.38 (95% CI 1.00-1.91). Safety results and actually delivered treatments revealed longer durations of treatment in the continuous arm, without significant unexpected findings.

Conclusion

Intermittent first-line treatment cannot be recommended in patients with HER2-negative advanced breast cancer.

Clinical trial registration: EudraCT 2010-021519-18; BOOG 2010-02.

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Acknowledgements

We thank all patients, physicians (research)nurses, and local data managers who participated in the Stop & Go trial; the members of the steering committee, the data safety monitoring committee, the central data management from the Comprehensive Cancer Centre the Netherlands, especially Steffen de Groot; and the Breast Cancer Research Group, especially Elise van Leeuwen – Stok. We are thankful to Harm van Tinteren for his statistical expertise and we thank the teams from F. Hoffmann-La Roche Ltd and TEVA Nederland B.V. for their support.

Funding

This study was funded by F. Hoffmann-La Roche Ltd, the Netherlands and TEVA Nederland B.V.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Zuyderland Medical Centre, Dr. H. van der Hoffplein 1, 6162 BG, Geleen, The Netherlands

    Anouk K. M. Claessens & Frans L. G. Erdkamp

  2. Department of Medical Oncology, Erasmus Medical Centre, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands

    Monique E. M. M. Bos

  3. Department of Biometrics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Marta Lopez-Yurda

  4. Department of Trial Registration, Comprehensive Cancer Centre the Netherlands, Vasteland 78, 3011 BN, Rotterdam, The Netherlands

    Jeanette M. Bouma

  5. Dutch Breast Cancer Research Group, BOOG Study Centre, IJsbaanpad 9, 1076 CV, Amsterdam, The Netherlands

    Jeany M. Rademaker-Lakhai

  6. Department of Medical Oncology, Isala Clinic, Dokter van Heesweg 2, 8025 AB, Zwolle, The Netherlands

    Aafke H. Honkoop

  7. Department of Medical Oncology, Leeuwarden Medical Centre, Henri Dunantweg 2, 8934 AD, Leeuwarden, The Netherlands

    Hiltje de Graaf

  8. Department of Oncologic Research, Reinier de Graaf Hospital, Reinier de Graafweg 5, 8934 AD, Delft, The Netherlands

    Edith van Druten

  9. Department of Medical Oncology, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands

    Laurence J. C. van Warmerdam & Maurice J. C. van der Sangen

  10. Department of Radiation Oncology, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands

    Maurice J. C. van der Sangen

  11. Department of Medical Oncology, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands

    Vivianne C. G. Tjan-Heijnen

  12. Department of Internal Medicine – Medical Oncology, Zuyderland Medical Centre, Dr. H. van der Hoffplein 1, 6162 BG, Geleen, The Netherlands

    Frans L. G. Erdkamp

Authors
  1. Anouk K. M. Claessens
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  2. Monique E. M. M. Bos
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  3. Marta Lopez-Yurda
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  6. Aafke H. Honkoop
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  7. Hiltje de Graaf
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  8. Edith van Druten
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  9. Laurence J. C. van Warmerdam
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  12. Frans L. G. Erdkamp
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The Dutch Breast Cancer Research Group (BOOG)

Corresponding author

Correspondence to Frans L. G. Erdkamp.

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Conflict of interest

FE has received honoraria from Roche and Novartis and has a consulting/advisory role for these companies. VTH has received honoraria from Pfizer, has a consulting or advisory role for Pfizer, Lilly, and Roche, has received research funding for her institution from Roche, Eisai, Pfizer, and Novartis, and has received travel, accommodations, and/or expenses from Pfizer, Novartis, and Roche. The authors declare that these are considered to be no major conflict of interest.

Ethical approval

The study was registered with EudraCT, number 2010-021519-18, and was conducted according to the International Conference on Harmonization (ICH) and Good Clinical Practice (GCP) guidelines, in agreement with the Declaration of Helsinki (version 1 May 1996) and local regulations (ethics committee Eindhoven, the Netherlands).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Data availability Additional data on the trial protocol can be found at the EU Clinical Trials Register, using number 2010-021519-18 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2010-021519-18). The datasets generated and analyzed during the current study are not publicly available due to ongoing data collection and (future) secondary endpoint analysis. Data, however, are available from the corresponding author on reasonable request.

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Claessens, A.K.M., Bos, M.E.M.M., Lopez-Yurda, M. et al. Intermittent versus continuous first-line treatment for HER2-negative metastatic breast cancer: the Stop & Go study of the Dutch Breast Cancer Research Group (BOOG). Breast Cancer Res Treat 172, 413–423 (2018). https://doi.org/10.1007/s10549-018-4906-8

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